1. Urinary bacteriophage cooperation with bacterial pathogens during human urinary tract infections supports lysogenic phage therapy.
- Author
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Almosuli M, Kirtava A, Chkhotua A, Tsveniashvili L, Chanishvili N, Irfan SS, Ng E, McIntyre H, Hockenberry AJ, Araujo RP, Zhou W, Vuong N, Birkaya B, Liotta L, and Luchini A
- Subjects
- Humans, Female, Urinary Tract Infections microbiology, Urinary Tract Infections therapy, Urinary Tract Infections virology, Lysogeny, Phage Therapy methods, Bacteriophages physiology, Bacteriophages genetics
- Abstract
Despite much promise in overcoming drug-resistant infections, clinical studies of bacteriophage antibacterial therapy have failed to show durable effectiveness. Although lysogeny plays an important role in bacterial physiology, its significance in diverse microbiomes remains unclear. Here, we tested the following hypotheses: 1) urinary microbiome phage populations switch to a higher relative proportion of temperate phages, and 2) the activity of the phage recombination machinery (integration/excision/transposition) is higher during human urinary tract infections (UTIs) than in non-infected urinary tracts. Using human urine, model organisms, mass spectrometry, gene expression analysis, and the phage phenotype prediction model BACPHLIP, the results corroborated our hypotheses at the functional protein and gene levels. From a human health perspective, these data suggest that temperate phages may facilitate bacterial infections rather than function as protective agents. These findings support the use of lysogenic phages as therapeutic Trojan Horses., Competing Interests: Competing interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LAL and AL are coinventors in granted patents US 9,012,240 and US 8,497,137, related to the affinity particles. The patents are owned by the George Mason Research Foundation. Ceres Nanosciences licensed the rights of the patents. LAL and AL own shares of Ceres Nanosciences. The remaining authors declared no competing interests., (© 2025. The Author(s).)
- Published
- 2025
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